1. Field of the Invention
The present invention relates, in general, to an extracellular signal regulated kinase, ERK-5. In particular, the present invention relates to nucleic acid molecules coding for ERK-5; ERK-5 polypeptides; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antisense ERK-5 nucleic acid constructs; antibodies having binding affinity to an ERK-5 polypeptide; hybridomas containing the antibodies; nucleic acid probes for the detection of ERK-5 nucleic acid; a method of detecting ERK-5 nucleic acid or polypeptide in a sample; kits containing nucleic acid probes or antibodies; a method of detecting a compound capable of binding to ERK-5 or a fragment thereof; a method of detecting an agonist or antagonist of ERK-5 activity; a method of agonizing or antagonizing ERK-5 associated activity in a mammal; a method of treating diabetes mellitus, skeletal muscle diseases, Alzheimer's disease, or peripheral neuropathies in a mammal with an agonist or antagonist of ERK-5 activity; and a pharmaceutical composition comprising an ERK-5 agonist or antagonist.
2. Background Information
Phosphorylation of serine/threonine residues on ribosomal protein S6 kinases (Ballou et al., J. Biol. Chem. 263:1188-1194 (1988)), phosphatase 1 G binding protein (Dent et al., Nature 348:302-308 (1990)), and acetyl coA-carboxylase (Borthwick et al., Biochem J. 270:795-801 (1990)) occur in response to insulin and other extracellular cues. Ray and Sturgill, Proc. Natl. Acad. Sci. USA 84:1502-1506 (1987), Cicirelli et al., J. Biol. Chem. 263:2009-2019 (1988), and Hoshi et al., J. Biol. Chem. 263:5396-5401 (1988) have identified a micro tubule-associated protein 2 (MAP2)/myelin basic protein (MBP) kinase that in response to insulin contains phosphate on serine/threonine residues (Ray and Sturgill, Proc. Natl. Acad. Sci. USA 85:3753-3757 (1988); Boulton et al., Cell 65:663-675 (1991)). Ribosomal protein S6 kinase has been identified as one potential target for this kinase (Sturgill et al., Nature 334:715-718 (1988); Gregory et al., J. Biol. Chem. 264:18397-18401 (1989); Ahn and Krebs, J. Biol. Chem. 265:11495-11591 (1990)). Boulton et al., Biochemistry 30:278-286 (1991) and Boulton et al., Science 249:64-65 (1990) describe the purification and cloning of a MAP2/MBP kinase which they named extracellular signal-regulated kinase 1 (ERK-1). Using probes derived from ERK-1, two novel kinases were identified, ERK-2 and ERK-3 (Boulton and Cobb, Cell Regulation 2:357-371 (May 1991); Boulton et al., Cell 65:663-675 (May 17, 1991)). A fourth ERK has been briefly described (Cobb et al., Cell Regulation 2:965-978 (December 1991) and WO 91/19008 published Dec. 12, 1991).
The present invention provides a novel ERK, ERK-5. ERK-5 shows 61% similarity (38% identity) to the human ERK1 peptide sequence, 64% similarity to the rat ERK1 and ERK2 (39% and 37% identity, respectively) and 55 % similarity to the rat ERK3 (30% identity).